This invention relates to a composition and method for treating helmintic infections. In one aspect, this invention is directed to the treatment of filarial infections.
Infestations with filarial helminths, such as the species Wucheria bancrofti, Onchocerca volvulus and the like, are quite common in West and Central Africa and in South and Central America. Similar species of filariae are also found in India, southern China, on the islands of Western Pacific, and in other regions. Studies have revealed that a major portion of the people living in the endemic areas of the foregoing regions are infected with these parasitic worms. Moreover, as a result of increased mobility of the people and the ease of air travel to and from regions where such parasitic infestations are endemic, these parasites may be transported by infected persons to, and may appear in, countries where they previously had been unknown.
One such filarial worm, Onchocerca volvulus, is very common all over West and Central Africa, and is believed to have been imported from there into Mexico, northeastern Venezuela, and Guatemala. The disease resulting from an infestation of this particular species, onchocerciasis, is a vector-borne disease that is transmitted via an insect bite. For example, infective larvae of this species can be introduced into the human body by the bite of the female black fly Simulium damnosum. The inoculated male and female larvae thereafter mature into worms which give rise to large numbers of microfilariae. The latter move freely through the dermal connective tissue of the infected individual and usually remain close to the skin surface in all regions of the human body. The biological cycle of O. volvulus is completed upon a subsequent uptake of microfilariae during an insect bite back into the insect vector where the microfilariae develop into infective larvae.
The most serious manifestations of this human disease are eye lesions which account for a high incidence of visual impairment and blindness in the endemic areas. Invasion of the corneal connective tissue by the microfilariae and their subsequent death leads to multiple discrete opacities and, in severe cases, to complete corneal opacification. In endemic regions where the intensity of the disease is particularly severe and where corneal opacification is extremely common, blindness due to onchocerciasis affects about 10 to about 30 percent of the population. In regions where the intensity of the disease is less severe and corneal opacification is less common, nevertheless onchocerciasis is associated with a high incidence of glaucoma in all age groups (including adolescents) and results in an incidence of blindness in about 10 percent of the population.
Elimination of onchocerciasis depends on either complete eradication of the infected insect vector or the destruction of the parasite in the human body. The vector control program initiated by the Word Bank and the World Health Organization has opted to pursue the former approach to control this disease in the Upper Volta basin; however, the program is very costly and the likelihood of its success is difficult to predict. The latter approach heretofore has utilized chemotherapy based on the oral administration of substantial doses of N,N-diethyl-4-methylpiperazine-1-carboxamide dihydrogen citrate (diethylcarbamazine or DEC).
However, such chemotherapy has considerable drawbacks inasmuch as the initial systemic reactions provoked by massive destruction of the microfilariae present may be quite severe and may require the administration of antihistamines or, in very severe cases, corticosteroids. In addition, observed side effects that are believed to be directly associated with the oral administration of diethylcarbamazine include headache, general malaise, weakness, joint pains, anorexia, nausea, and vomiting. Other untoward responses also have been reported. For example, in patients with onchocerciasis there is usually a violent reaction within about 16 hours after administration of the first oral dose. This reaction includes swelling and edema of the skin, intense itching, enlargement and tenderness of the inguinal lymph nodes, sometimes a fine papular rash, hyperpyrexia up to 102.degree. F., tachychardia and headache. These symptoms can persist for about 3 to about 7 days, and, of course, have a debilitating effect on the patient.
The foregoing untoward side effects notwithstanding, diethylcarbamazine has been widely used as an oral chemotherapeutic against filarial infections since the late 1940's. When orally administered daily for a period of several weeks, diethylcarbamazine decreases the skin count of the microfilariae of O. volvulus to very low levels. However, such a treatment fails to kill the parent parasitic worm, and cessation of the oral chemotherapy results in a rapid resurgence of microfilarial density in the skin.
Accordingly, there exists a need for a more effective treatment of helmintic infections, in particular of onchocerciasis, and for means to effect such treatment.